Deficiency of electroneutral K+-Cl- cotransporter 3 causes a disruption in impulse propagation along peripheral nerves

Yuan Ting Sun, Thy Sheng Lin, Shun Fen Tzeng, Eric Delpire, Meng Ru Shen

研究成果: Article同行評審

18 引文 斯高帕斯(Scopus)

摘要

Nerve conduction requires the fine tuning of ionic currents through delicate interactions between axons and Schwann cells. The K+-Cl - cotransporter (KCC) family includes four isoforms (KCC1-4) that play an important role in the maintenance of cellular osmotic homeostasis via the coupled electroneutral movement of K+ and Cl- with concurrent water flux. Mutation in SLC12A6 gene encoding KCC3 results in an autosomal recessive disease, known as agenesis of the corpus callosum associated with peripheral neuropathy. Nevertheless, the role of KCC3 in nerve function remains a puzzle. In this study, the microscopic examination of KCC isoforms expressed in peripheral nerves showed high expression of KCC2-4 in nodal segments of the axons and in the perinucleus and microvilli of Schwann cells. The KCC inhibitor [[(dihydroindenyl)oxy]alkanoic acid] but not the Na +-K+-2Cl--cotransport inhibitor (bumetanide) dose-dependently suppressed the amplitude and area of compound muscle action potential, indicating the involvement of KCC activity in peripheral nerve conduction. Furthermore, the amplitude and area under the curve were smaller, and the nerve conduction velocity was slower in nerves from KCC3-/- mice than in nerves from wild-type mice, while the expression pattern of KCC2 and KCC4 was similar in KCC3 kockout and wild-type strains. KCC3-/- mice also manifested a prominent motor deficit in the beam-walking test. This is the first study to demonstrate that the K+-Cl- cotransporter activity of KCC3 contributes to the propagation of action potentials along peripheral nerves.

原文English
頁(從 - 到)1544-1552
頁數9
期刊GLIA
58
發行號13
DOIs
出版狀態Published - 2010 10月

All Science Journal Classification (ASJC) codes

  • 神經內科
  • 細胞與分子神經科學

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